Impact of whole body irradiation and vascular endothelial growth factor-A on increased beta cell mass after bone marrow transplantation in a mouse model of diabetes induced by streptozotocin.
OBJECTIVE
Recent studies have shown that bone marrow transplantation reduces hyperglycaemia in a mouse model of diabetes induced by streptozotocin. However, the essential factors for the improvement of hyperglycaemia by bone marrow transplantation have not been fully elucidated. The aim of this study was to search for such factors.


METHODS
We investigated the effect of irradiation to whole body, to abdomen alone or to whole body excluding abdomen, followed by infusion or no infusion of bone marrow cells. We also investigated the effect of bone marrow transplantation on beta cell-specific vascular endothelial growth factor-A gene (Vegfa) knockout mice.


RESULTS
Bone marrow transplantation improved streptozotocin-induced hyperglycaemia and partially restored islet mass. This change was associated with increased islet vascularisation. Among the other methods investigated, low-dose irradiation of the whole body without infusion of bone marrow cells also improved blood glucose level. In streptozotocin-treated beta cell-specific Vegfa knockout mice, which exhibit impaired islet vascularisation, bone marrow transplantation neither improved hyperglycaemia, relative beta cell mass nor islet vascularisation.


CONCLUSIONS
Our results indicate that whole body irradiation is essential and sufficient for restoration of beta cell mass after streptozotocin treatment independent of infusion of bone marrow cells. Vascular endothelial growth factor-A produced in beta cells is also essential for this phenomenon.
Nakayama
S
S
Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo, Japan.
Uchida
T
T
Choi
J B
JB
Fujitani
Y
Y
Ogihara
T
T
Iwashita
N
N
Azuma
K
K
Mochizuki
H
H
Hirose
T
T
Kawamori
R
R
Inoue
M
M
Watada
H
H
D000818:Animals; D016026:Bone Marrow Transplantation; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000517:prevention & control; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014185:Transplantation, Isogeneic; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014916:Whole-Body Irradiation
D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse